[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-563618-105":3,"detail-sidebar-cat-1-en-105":81,"doc-detail-563618-en":127},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","mots-c-evidence-summary","MOTS-c - Evidence Summary","","Cognitive Vitality Reports ® summarize neuroscientist-led evidence on MOTS-c, a mitochondrial derived peptide, focusing on metabolic flexibility, insulin sensitivity, and potential anti-inflammatory neuroprotective effects. The report reviews drug discovery components including drug targets, supplements, mechanistic pathways, and risk factors related to brain health and age-associated conditions. It evaluates available safety and translational findings from clinical and preclinical evidence, noting unmet needs in effective clinical delivery and established limitations for therapeutic use in CNS contexts.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/template/","Template",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/template/general/","General",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/template/mots-c-evidence-summary/563618/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/mots-c-evidence-summary/563618.png","ImageObject",442,249,{"name":42,"@type":43},"Jordan Avery","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-31","2026-10-12",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",6,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What does MOTS-c promote according to the report?","Question",{"text":63,"@type":64},"MOTS-c promotes metabolic flexibility and insulin sensitivity. It is also described as potentially exerting anti-inflammatory effects and supporting cellular energetics.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Is MOTS-c expected to work as a CNS therapeutic?",{"text":68,"@type":64},"No. MOTS-c is not BBB penetrant, and centrally administered or intranasal delivery with a cell-penetrating carrier is required to see protective effects in preclinical memory models.",{"name":70,"@type":61,"acceptedAnswer":71},"What safety information is provided?",{"text":72,"@type":64},"MOTS-c therapeutic safety has not been established. An analog, CB4211, was safe in a short-term study, but persistent injection site reactions were common, and MOTS-c may interact with other AMPK-targeting drugs.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},563618,1792087353,{"code":4,"msg":82,"data":83},"success",[84,89,94,99,104,109,114,119,124],{"id":85,"doc_module":22,"doc_module_name":25,"category_name":86,"show_sort_weight":87,"slug":88},11,"Presentations",90,"presentations",{"id":90,"doc_module":22,"doc_module_name":25,"category_name":91,"show_sort_weight":92,"slug":93},12,"Resumes",80,"resumes",{"id":95,"doc_module":22,"doc_module_name":25,"category_name":96,"show_sort_weight":97,"slug":98},14,"Invoices",70,"invoices",{"id":100,"doc_module":22,"doc_module_name":25,"category_name":101,"show_sort_weight":102,"slug":103},15,"Posters",60,"posters",{"id":105,"doc_module":22,"doc_module_name":25,"category_name":106,"show_sort_weight":107,"slug":108},16,"Social Media",50,"social-media",{"id":110,"doc_module":22,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},17,"Forms",40,"forms",{"id":115,"doc_module":22,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},18,"Letters",30,"letters",{"id":120,"doc_module":22,"doc_module_name":25,"category_name":121,"show_sort_weight":122,"slug":123},21,"Paper Templates",5,"papers-templates",{"id":125,"doc_module":22,"doc_module_name":25,"category_name":29,"show_sort_weight":4,"slug":126},158,"general-158",{"code":4,"msg":82,"data":128},{"doc_id":79,"user_id":129,"nickname":42,"user_avatar":130,"doc_module":22,"category_id":125,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":131,"file_id":132,"file_url":133,"file_type":134,"file_size":135,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":136,"language":137,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":138,"faqs":139,"seo_title":140,"seo_description":12,"update_tm":141,"read_time":142},1099523882367,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","Cognitive Vitality Reports ® are reports written by neuroscientists at the Alzheimer’s Drug Discovery Foundation (ADDF). These scientific reports include analysis of drugs, drugs-indevelopment, drug targets, supplements, nutraceuticals, food/drink, non-pharmacologic interventions, and risk factors. Neuroscientists evaluate the potential benefit (or harm)for brain health, as well as for age-related health concerns that can affect brain health (e.g., cardiovascular diseases, cancers, diabetes/metabolic syndrome). In addition, these reports include evaluation of safety data, from clinical trials if available, and from preclinical models.  \nMOTS-c  \nEvidence Summary  \nMOTS-c promotes metabolic flexibility and insulin sensitivity. Endogenous levels decline with age. Supplementation may have rejuvenating effects, but effective clinical translation has been lacking thus far.  \nNeuroprotective Benefit: MOTS-c may have anti-inflammatory properties and promote cellular energetics, but is not BBB penetrant.  \nAging and related health concerns: MOTS-c enhances metabolic flexibility, improves insulin sensitivity, and may act as an exercise mimetic. MOTS-c rejuvenates aging phenotypes in muscle in mice, but its translational potential is currently limited.  \nSafety: MOTS-c therapeutic safety has not been established. The analog CB4211 was safe in a short-term study, but persistent injection site reactions were common. MOTS-c may interact with other drugs that target AMPK.  \n\n| Availability: Research use | Dose: Not established | Chemical formula:\u003Cbr>C101 H152 N28O22S2\u003Cbr>MW: 2174.6 g/mol\u003Cbr>Sequence: H-Met-Arg-Trp-GlnGlu-Met-Gly-Tyr-Ile-Phe-TyrPro-Arg-Lys-Leu-Arg-OH |\n| --- | --- | --- |\n| Half-life: N/A | BBB: Not penetrant |  |\n| Clinical trials: MOTS-c analog CB4211 was tested in in Phase 1a/1b (n=88) . | Observational studies: Endogenous MOTS-c levels decline with age and in populations with metabolic dysfunction. |  |\n\nWhat is it?  \nMitochondrial ORF of the 12S ribosomal RNA type-c (MOTS-c) is a 16 amino acid mitochondrial derived peptide (MRWQEMGYIFYPRKLR) encoded by a short open reading frame within 12S rRNA located in the mitochondrial genome (mtDNA) [2] . It is involved in the regulation of cellular bioenergetic homeostasis. MOTS-c is translated within the cytosol using the standard genetic code. It acts as a metabolic regulator primarily through activation of the AMP-activated kinase (AMPK), leading to an increase in lipid metabolism and cellular glucose flux. Skeletal muscle is the primary target organ of MOTS-c, where it acts to improve metabolic flexibility. It is not currently available for therapeutic use, but is used illegally as a performance enhancing drug by athletes [6] .  \nCB411 is a MOTS-c peptide analog developed by CohBar, which was tested in a Phase 1a/1b trial in healthy volunteers along with a cohort with obesity and fatty liver disease ( NCT03998514) . CohBar also developed mitochondrial derived peptide analog-based therapeutics that were tested in preclinical models of obesity, fibrotic disease, and cancer. However, clinical development of CB411 has been discontinued due to the dissolution of CohBar.  \nIn the intervening time, other companies have not yet emerged to continue development on mitochondrial derived peptide analog-based therapeutics, which likely stems from the technical challenges of this approach.  \nNeuroprotective Benefit: MOTS-c may have anti-inflammatory properties and promote cellular energetics, but is not BBB penetrant.  \nTypes of evidence:  \n• 2 laboratory studies  \nHuman research to suggest prevention of dementia, prevention of decline, or improved cognitive function? None  \nHuman research to suggest benefits to patients with dementia: None  \nMechanisms of action for neuroprotection identified from laboratory and clinical research: The potential role of endogenous MOTS-c in the brain is unclear, but may play a role in regulating metabolism [2] . At a dose that improved physical capacity, pe","cbCaio59jWfNwPpB","https://ap.wps.com/l/cbCaio59jWfNwPpB","pdf",552537,19,"English","# MOTS-c - Evidence Summary\n## What is it?\n## Neuroprotective Benefit\n## Aging and related health concerns\n## Safety\n## Types of evidence and evidence gaps\n## Mechanisms of action and study outcomes\n## Challenges for clinical translation","[{\"question\":\"What does MOTS-c promote according to the report?\",\"answer\":\"MOTS-c promotes metabolic flexibility and insulin sensitivity. It is also described as potentially exerting anti-inflammatory effects and supporting cellular energetics.\"},{\"question\":\"Is MOTS-c expected to work as a CNS therapeutic?\",\"answer\":\"No. MOTS-c is not BBB penetrant, and centrally administered or intranasal delivery with a cell-penetrating carrier is required to see protective effects in preclinical memory models.\"},{\"question\":\"What safety information is provided?\",\"answer\":\"MOTS-c therapeutic safety has not been established. An analog, CB4211, was safe in a short-term study, but persistent injection site reactions were common, and MOTS-c may interact with other AMPK-targeting drugs.\"}]","MOTS-c - Evidence Summary | PDF",1791836866,7]